title: Triptolide ameliorates Crohn's colitis is associated with inhibition of TLRs/NF-κB signaling pathway.
abstract: Growing evidence suggests that TLRs/NF-κB signaling pathway plays a critical role in the pathogenesis of Crohn's disease (CD). We have reported that triptolide, an active component from Tripterygium wilfordii Hook, showed therapeutic activity in IL-10-deficeint (IL-10-/- mice, a murine CD model. However the full mechanisms of action of this agent in CD remain largely unknown. We hypothesized that triptolide would ameliorate the experimental colitis by inhibiting TLRs/NF-κB signaling pathway. We found TLR2 and TLR4 were upregulated in IL-10-)/- mice, triptolide inhibited the TLRs/NF-κB signaling pathway in vivo. In addition, triptolide in vitro was able to downregulate the TLRs/NF-κB pathway in cultured colonic explants from CD patients. Our results confirm the therapeutic effect of triptolide in experimental colitis, and suggest it as a promising compound for CD treatment. These findings also support the possibility that targeted inhibition of TLR signaling pathway is an approach deserving further investigation as a therapeutic strategy for CD.
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China
authors.forename: Chao
authors.initials: C
authors.lastname: Yu
authors.forename: Ting
authors.initials: T
authors.lastname: Shan
authors.forename: Aiwen
authors.initials: A
authors.lastname: Feng
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Weiming
authors.initials: W
authors.lastname: Zhu
authors.forename: Ying
authors.initials: Y
authors.lastname: Xie
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Jieshou
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D003424:Crohn Disease / Q000188:drug therapy*; D004224:Diterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D004852:Epoxy Compounds / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D046509:Tissue Culture Techniques; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D029757:Tripterygium
chemical_list: D004224:Diterpenes; D004852:Epoxy Compounds; C556062:IL10 protein, mouse; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D010616:Phenanthrenes; D010936:Plant Extracts; D051193:Toll-Like Receptors; D051996:Transcription Factor RelA; D016753:Interleukin-10; C001899:triptolide